Eltrombopag for Treatment of Thrombocytopenia Following Hematopoietic Stem Cell Transplantation

Objective: This study aimed to evaluate the efficacy and safety of eltrombopag (ELT) in the treatment of thrombocytopenia following hematopoietic stem cell transplantation (HSCT). Materials and Methods: Forty-eight patients treated with ELT for thrombocytopenia after allogeneic or autologous transplantation at the Erciyes University Bone Marrow Transplantation Center between July 2017 and July 2021 were evaluated retrospectively. Results: Forty-eight HSCT recipients were included in this study. Thirty (62.5%) patients were evaluated as having experienced delayed platelet recovery (DPR) and 18 (37.5%) patients as having experienced secondary failure of platelet recovery (SFPR). The median platelet count before ELT treatment was 13x109/L (range: 3-20x109/L). Twenty-three patients responded to treatment and the cumulative incidence of successful platelet recovery was 48%. Patients with both DPR and SFPR responded, but patients with DPR had a higher response rate (50% vs. 44%). The median platelet count of the 23 responding patients was 12x109/L (5-19x109/L) before treatment and 68x109/L (52-266x109/L) after treatment (p<0.0001). While the number of bone marrow megakaryocytes before treatment was adequate in 22 (46%) cases, it was decreased in 26 (54%) cases. Patients with adequate bone marrow megakaryocytes had a better response rate than those without (77% vs. 23%, p<0.0001). The group with adequate megakaryocytes responded to treatment at a median of 33 days (range: 9-174 days). Patients with decreased megakaryocytes responded at a median of 55 days (30-164 days) (p=0.002). No drug-related side effects were observed in any patients. Conclusion: This real-life experience demonstrates that ELT is an effective and safe treatment option for thrombocytopenia after HSCT. The adequacy of bone marrow megakaryocytes before ELT treatment was an important factor affecting response to treatment.

Pre-Conditioning Serum Uric Acid as a Risk Factor for Sinusoidal Obstruction Syndrome of the Liver in Children Undergoing Hematopoietic Stem Cell Transplantation

Objective: Uric acid (UA), a known danger signal released from injured cells, is a valuable sign of inflammation. We aimed to evaluate the association of serum UA levels before the start of conditioning regimens with the risk of hepatic sinusoidal obstruction syndrome (SOS) development after hematopoietic stem cell transplantation (HSCT). Materials and Methods: Two hundred and twenty-two children who underwent allogeneic HSCT at the Pediatric BMT Unit of Hacettepe University between 2000 and 2014 were included in this retrospective study. Serum UA levels were measured before conditioning as an indicator of the pre-transplant inflammatory status of the patients. Patients with and without a diagnosis of SOS were compared regarding primary diagnosis, previously described risk factors for SOS, and pre-conditioning serum UA. Results: SOS was diagnosed in 42 patients who had higher pre-conditioning serum UA levels compared to those who did not. Pre-transplant serum creatinine, gamma-glutamyl transferase, bilirubin, ferritin, and C-reactive protein levels did not differ significantly among patients with and without SOS; however, serum albumin was lower in the patients who developed SOS. Receiver operating characteristic analysis revealed that a pre-conditioning UA level higher than 3.32 mg/dL was predictive of SOS. When applied to a multivariate model, only pre-conditioning UA and albumin levels remained significant risk factors for SOS (UA: odds ratio [OR], 2.54; 95% confidence interval [CI], 1.26-5.12, p=0.009; albumin: OR, 0.45, 95% CI, 0.22-0.95, p=0.037). Conclusion: Our results suggest that pre-conditioning serum UA is an independent risk factor for SOS, and it might be used as an early predictor of hepatic SOS together with previously described clinical and laboratory parameters.

Immune reconstitution after T-cell replete HLA haploidentical hematopoietic stem cell transplantation using high-dose post-transplant cyclophosphamide.

As HLA haploidentical related donors are quickly available, HLA haploidentical hematopoietic stem cell transplantation (haploHSCT) using high-dose post-transplant cyclophosphamide (PTCy) is now widely used. Recent basic and clinical studies revealed the details of immune reconstitution after T-cell replete haploHSCT using PTCy. T cells and NK cells in the graft proliferate abundantly at day 3 post-haploHSCT, and the PTCy eliminates these proliferating cells. After ablation of proliferating mature cells, donor-derived NK cell reconstitution occurs after the second week; however, recovering NK cells remain functionally impaired for at least several months after haploHSCT. PTCy depletes proliferating cells, resulting in the preferential accumulation of Treg and CD4+ T cells, especially the memory stem T cell (TSCM) phenotype. TSCM capable of both self-renewal and differentiation into effector T cells may play an important role in the first month of immune reconstitution. Subsequently, de novo T cells progressively recover but their levels remain well below those of donor CD4+ T cells at the first year after haploHSCT. The phenotype of recovering T cells after HSCT is predominantly effector memory, whereas B cells are predominantly phenotypically naive throughout the first year after haploHSCT. B cell recovery depends on de novo generation and they are not detected until week 4 after haploHSCT. At week 5, recovering B cells mostly exhibit an unconventional transitional cell phenotype and the cell subset undergoes maturation. Recent advances in immune reconstitution have improved our understanding of the relationship between haploHSCT with PTCy and the clinical outcome.

Bone marrow mesenchymal stem cell transplantation for treatment of diabetes:“transdifferantiation”appears? / 中国组织工程研究

BACKGROUND:In recent years a large number of studies have suggested that bone marrow mesenchymal stem cells can ease hyperglycemia of diabetic rats, but the related mechanism is unclear and controversial. OBJECTIVE:To investigate the relevant mechanism of bone marrow mesenchymal stem cells on pancreas microenvironment in vivo in diabetic rats. METHODS:Bone marrow mesenchymal stem cells were transfected with enhanced green fluorescent protein (EGFP) and administered to diabetic rats via the subcapsular pancreas. Blood glucose levels were monitored. The expressions of the key genes in islet development in these EGFP positive pancreatic cells were analyzed by Real-time quantitative PCR at different times. EGFP and insulin double-positive cells were detected by immunofluorescence. Flow cytometry was performed to analyze cellcycle and DNA ploidy. RESULTS AND CONCLUSION:Blood glucose levels were effectively reduced after transplantation. The expressions of the key genes in islet development reached their own peak values at different times after transplantation:Nestin at week 1, Nkx 2.2 at week 3, Pax 4 and Ngn 3 at week 4, insulin and glucagon at week 12, PDX-1 at week 8 until week 12. The cells double-positive for EGFP and insulin cells were observed. In the pancreas, EGFP positive cells at S+G 2/M phase were significantly increased, and there were no polyploid and aneuploid cells. In pancreas microenvironment, the bone marrow mesenchymal stem cells transplanted into the diabetic pancreas can differentiate into isletβ-like cells under gene control, but not through the fusion with tissue cells.

Stem cell transplantation for spinal cord injury:prospects and issues / 中国组织工程研究

BACKGROUND:At present, spinal cord injury treatment is stil the worldwide difficult problem. Using the method of stem cells transplantation to treat the spinal cord injury is one of the hotspots of spinal cord injury repair research in recent years. OBJECTIVE:To summarize the progress and application prospects of stem celltransplantation in the treatment of spinal cord injury. METHODS:A computer-based search of PubMed and CNKI was retrieved for relevant articles concerning stem celltransplantation for treatment of spinal cord injury published after 2000. The keywords were“spinal cord injury, stem cell, celltherapy”in English and Chinese, respectively. Meta-analysis and secondary literature were excluded as wel as repetitive or old literature. Final y, 52 articles were included in result analysis. RESULTS AND CONCLUSION:This article summarizes types and biological characteristics of stem cells, basic mechanism, techniques and therapeutic efficacy of stem celltransplantation in the treatment of spinal cord injury, and proposes the issues and prospects concerning the stem cells transplantation for treatment of spinal cord injury.

Transplantation of bone marrow mesenchymal stem cells transfected by vascular endothelial growth factor gene promotes foot wound healing in diabetic rats / 中国组织工程研究

BACKGROUND:Diabetic foot ulcers threaten the patients’ health and even survival seriously. It is an international difficult problem and lacks an effective treatment. But gene therapy and stem celltherapy possess special advantages and potential in wound healing. OBJECTIVE:To assess the therapeutic effect of transplantation of bone marrow mesenchymal stem cells transfected by human vascular endothelial growth factor 165 (hVEGF165) gene on foot wound healing in diabetic rats. METHODS:Recombinant adenovirus was established in vitro which expressed hVEGF165 gene and transfected into the third generation of bone marrow mesenchymal stem cells. Total y 120 male Wistar rats were divided into five groups:group A (non-diabetic controls), group B (diabetic controls), group C (Ad-hVEGF165 therapy), group D (stem celltherapy) and group E (transplantation of bone marrow mesenchymal stem cells transfected by Ad-hVEGF165 gene). Rats in the latter four groups were intraperitoneal y injected with streptozotocin to induce diabetic models. In al rats, a 3 mm×7 mm rectangular ful-thickness skin sample was cut from the instep of the hind foot to make a model of foot wound. The rats were subcutaneously injected at equidistant six points 5 mm distal to the wound edge on the dorsum of the foot:50μL PBS per point for group A, 50μL adenovirus suspension (1×1013 pfu/L) per point for group C, 50μL stem cellsuspension (1×1010/L) per point for group D, and 50μL adenovirus suspension+50μL stem cellsuspension per point for group E. RESULTS AND CONCLUSION:After injection, the rate of wound healing, the expression of VEGF and the qualities of capil aries in group E were higher when compared with groups B, C, D (P<0.05), but were lower than those in group A (P<0.05). Transplantation of bone marrow mesenchymal stem cells transfected by hVEGF165 gene can promote foot wound healing, angiogenesis and expression of VEGF in diabetic rats.

Allogeneic bone marrow mesenchymal stem cell transplantation for acute myocardial infarction in rats / 中国组织工程研究

BACKGROUND:A number of studies have shown that bone marrow mesenchymal stem cells can survive in the infarcted myocardium and improve cardiac function. OBJECTIVE:To investigate the effects of al ogeneic rat bone marrow mesenchymal stem cells on heart failure in acute myocardial infarction models of rats and possible mechanisms. METHODS:Rat bone marrow mesenchymal stem cells were isolated from the bone marrow of 39 male Wistar rats by density gradient centrifugation with Percol . After ligating anterior descending coronary artery, 39 female Wistar rats were randomly divided into three groups:control group (Dulbecco’s modified Eagle’s medium, n=12), mesenchyma stem cells group (n=15) and mononuclear cells group (n=12). Eight weeks later, hemodynamics and left ventricular function were measured. Histopathological and immunohistochemical examinations were performed. RESULTS AND CONCLUSION:Compared with the control group, left ventricular end diastolic pressure, left ventricular relative weight, the col agen volume fraction of type I and type III in the infarction zone of the left ventricle were al significantly decreased, in contrast to ±dp/dtmax,-dp/dtmax/left ventricular systolic pressure, body weight and vascular density in infarction zone were al significantly increased both in mesenchymal stem cells group and mononuclear cells group. There were no significant differences between two treatment groups except for interventricular septal thickness and vascular density in non-infarction zone. 5-Bromo-2'-deoxyuridine positive cells were observed in the infarction area of mesenchyma stem cells group but no positive cells in mononuclear cells group. Some bal-like cellmasses were found positively stained with desmin and cardiac troponin T. Results have suggested that embedded bone marrow mesenchymal stem cells survived in exogenous host hearts. The therapy of mononuclear cells and mesenchymal stem cells could limit the left ventricular remodeling after acute myocardial infarction and improve left ventricular function through angiogenesis inducing and col agen deposition decreasing.

Effects of basic fibroblast growth factor via coronary venous retroperfusion on bone marrow mesenchymal stem cell differentiation in vivo / 中国组织工程研究

BACKGROUND:In vitro studies have demonstrated that basic fibroblast growth factor (bFGF) promote the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cardiomyocyte-like cells. However, it is unclear whether coronary venous retroperfusion of bFGF stimulates BMSCs differentiation in vivo. OBJECTIVE:To evaluate the effects of coronary venous retroperfusion of bFGF on BMSCs differentiation in vivo. METHODS:BMSCs from 12 dogs were isolated by density gradient centrifugation and expanded in vitro. These cells were transfected by enhanced green fluorescence protein (EGFP) lentiviral vector and the transfection efficiency was analyzed. Acute myocardial infarction was induced by ligation of left anterior descending coronary artery. After 1 week, 10 survival animals were randomized to BMSCs group (n=5) and bFGF+BMSCs group (n=5). bFGF-and EGFP-positive BMSCs were reversely infused via coronary vein using over-the-wire bal oon catheter. One week after infusion, the number of EGFP-positive cells co-staining factor VIII and troponin I was compared between the two groups by immunofluorescence method. RESULTS AND CONCLUSION:BMSCs were successful y transfected by EGFP and the transfection efficiency was 85%. Immunofluorescence showed that EGFP-positive BMSCs were observed in 23.5%of slides. There were more EGFP-positive cells co-staining VIII and troponin I in the bFGF+BMSCs group than in the BMSCs group (P<0.05). Thus, the coronary venous retroperfusion of bFGF enhances the differentiation of BMSCs into vascular endothelial cells and cardiomyocytes. Combined delivery of bFGF and BMSCs can exert a synergistic effect to promote cardiac repair.

Intranasal delivery of bone marrow mesenchymal stem cells for brain injuries:how many questions to be verified? / 中国组织工程研究

BACKGROUND:Transplantation of bone marrow mesenchymal stem cells can promote repair of brain injuries in animals. OBJECTIVE:To summarize the research progress in intranasal delivery of bone marrow mesenchymal stem cells to the brain. METHODS:A computer-based online retrieval of PubMed and Wanfang databases was performed to search papers published during January 1999 to January 2014 with the key words of“bone marrow mesenchymal stem cells, brain injury, transplantation”in English and Chinese. Thirty-eight papers were included in the final analysis. RESULTS AND CONCLUSION:Nowadays, many studies have been certified that the transplantation of bone marrow mesenchymal stem cells can significantly ameliorate the function of cranial nerve in animal models of brain injury. Many researchers have searched for the transplantation methods and approaches and have made progresses in many aspects. In this article, we compare the different transplantation ways of bone marrow mesenchymal stem cells to the brain. We focus on the intranasal transplantation route in the fol owing aspects:processing of the nasal mucosa;delivery route to the brain;labeling and intracranial observation of stem cells;animal experiments. We conclude that the intranasal delivery of bone marrow mesenchymal stem cells to the brain has a wide clinical application as a noninvasive transplantation.

Survival of bone marrow mesenchymal stem cells after transplantation into the rat infarcted myocardium / 中国组织工程研究

BACKGROUND:The preliminary findings confirm that bone marrow mesenchymal stem celltransplantation is safe and effective in the treatment of acute myocardial infarction, but its exact mechanism is unclear. There are few studies addressing the survival status of transplanted stem cells and its acting timing. OBJECTIVE:To study the survival of rat bone marrow mesenchymal stem cells transplanted into the infracted myocardium. METHODS:Bone marrow mesenchymal stem cells were cultured using density gradient centrifugation. Eighty rat models of myocardial infarction were prepared. Bone marrow mesenchymal stem cells were injected via a microsyringe at four sites around the infarcted region at 14 days after modeling. Then, 70 rats with living cells were selected for detecting the survival of bone marrow mesenchymal stem cells at days 3, 5, 7, 10, 20, 28 after transplantation. RESULTS AND CONCLUSION:Under ×400 visual field, the number of Brdu-positive bone marrow mesenchymal stem cells was (36±12) at 3 days posttranplantation, (33±13) at 5 days, (28±9) at 7 days, (15±5) at 10 days, (5±3) at 14 days, 0 at 20 days, and 0 at 28 days, showing a overal downward trend after transplantation. The number of bone marrow mesenchymal stem cells was negatively correlated with transplant days (P<0.01, r=-0.47). The number of cells decreased most significantly within 1 week after transplantation, and then decreased to 0 at 20 days. These findings indicate that transplanted bone marrow mesenchymal stem cells in the myocardium cannot survive for a long term and also cannot be transformed into myocardial tissue.

Intrathecal injection of umbilical cord mesenchymal stem cells for spinocerebellar ataxia / 中国组织工程研究

BACKGROUND:Spinocerebel ar ataxia is a inherited neurodegenerative disease with progressive cerebel ar masonic movement disorders as the main clinical manifestation. So far, no drug is available to control the disease progression. OBJECTIVE:To observe the clinical effect of umbilical cord mesenchymal stem cells in treating spinocerebel ar ataxia by intrathecal injection. METHODS:Thirty-eight cases of spinocerebel ar ataxia were given umbilical cord mesenchymal stem cells by intrathecal injection, 1×106/kg once a week, four times as a course. These 38 cases received 52 courses. Among them, 27 cases received 1 course, 8 cases received 2 courses and 3 cases received 3 courses. International Cooperative Ataxia Rating Scale (ICARS) and Activity of Daily Living Scale (ADL) were used to evaluate patients’ neural functions (the greater scores, the more severe damage) and ability of daily living (the lower score, the stronger the ability of daily living). After treatment, al patients were subjected to fol ow-up visit. RESULTS AND CONCLUSION:The total effective rate of 52 courses of treatment was 84.62%. ICARS and ADL scores were significantly decreased at 1 month after treatment (P<0.01). In most of effective patients, unstable walking and standing, slow movement, upper limb fine motor disorder, writing difficulties, dysarthria, eye movement disorders were improved. After treatment, common adverse effects were dizziness (1 case), low back pain (2 cases), headache (1 case), and fever (2 cases). Al these symptoms disappeared within 1-3 days. No treatment-related adverse events happened in the median fol ow-up of 39 months (11-59 months). The il ness of effective patients had been stable for 1-19 months, average (5.95±4.84) months. Intrathecal injection of umbilical cord mesenchymal stem cells is safe to ameliorate clinical symptoms to some extent within a certain time. It may delay the progression of spinocerebel ar ataxia. Multiple courses of treatment can help to further improve neurological function in most patients.

Relationship between CD4+CD25+FOXP3+Treg cells and acute graft-versus-host disease / 中国组织工程研究

BACKGROUND:The CD4+CD25+FOXP3+Treg cells have immunosuppression effect, and it is speculated that these cells may restrain the occurrence of acute graft-versus-host disease. OBJECTIVE:To observe the variety of the CD4+CD25+FOXP3+Treg cells in the peripheral blood from donors before and after granulocyte colony stimulating factor mobilization, and study the relationship between CD4+CD25+FOXP3+Treg cells and acute graft-versus-host disease. METHODS:Ninety patients with malignant blood diseases who undertook al ogeneic hematopoietic stem celltransplantation and their donors were observed. Granulocyte colony stimulating factor 5μg/kg was injected subcutaneously into the donor per 12 hours for 5 days, and the stem cells were col ected before and after mobilization. The ratio of CD4+CD25+FOXP3+Treg cells in the peripheral blood was detected before and after mobilization with flow cytometry, and the ratio of these cells in the stem cellsuspension was measured by the same method. The patients were divided into two groups according to the CD4+CD25+FOXP3+Treg cells ratio:high dosage group (≥5%) and low dosage group (<5%). The incidence of acute graft-versus-host disease was observed in the two groups after transplantation. RESULTS AND CONCLUSION:The ratio of the CD4+CD25+FOXP3+Treg cells in the donor before and after mobilization were 11.3%and 1.5%,respectively, and there was a significant difference (P<0.05). The ratio of the CD4+CD25+FOXP3+Treg cells was 3.4%in the patients with acute graft-versus-host disease, and 15.7%in the patients with no acute graft-versus-host disease, showing a significant difference (P<0.05). After hematopoietic reconstitution, the incidence of acute graft-versus-host disease was 18.4%in the high dosage group and 48.1%in the low dosage group, and there was a significant difference between the two groups (P<0.05). Therefore, the granulocyte colony stimulating factor can lower the ratio of CD4+CD25+FOXP3+Treg cells in the human peripheral blood. The increase in CD4+CD25+FOXP3+Treg cells can restrain the occurrence of acute graft-versus-host disease.

Blood glucose recovery following allogenetic hematopoietic stem cell transplantation in patients with hematological diseases complicated with diabetes mellitus / 中国组织工程研究

BACKGROUND:Recent studies have shown that the large-dose regular insulin therapy used to control blood glucose levels can cause 50%of patients suffering from vascular, optic nerve and kidney complications. Previous results from authors exhibit that when al ogeneic hematopoietic stem celltransplantation is applied for treatment of leukemia, diabetic symptoms in patients disappear. Dose it prompt that al ogeneic hematopoietic stem celltransplantation is an effective therapy for treatment of diabetes mel itus? OBJECTIVE:To explore the feasibility of hematopoietic stem celltransplantation for treatment of diabetes mel itus. METHODS:A retrospective analysis was done regarding the data of patients with hematological diseases complicated with diabetes mel itus who underwent al ogenetic hematopoietic stem celltransplantation. Four patients with acute lymphocyte leukemia, chronic myelogenous leukemia, aplastic anemia, and myolodysplastic syndromes, respectively, were complicated with diabetes mel itus. Conditioning regimen was cyclophosphamide+total body irradiation protocol. Cyclosporin A and short-term methotrexate were used for graft-versus-host disease prophylaxis. Blood glucose was control ed by oral hypoglycemic drugs or insulin injections before transplantation. RESULTS AND CONCLUSION:Al the four patients were successful y engrafted. Fasting glucose level of the four patients recovered at 4-6 months after hematopoietic stem celltransplantation (without hypoglycemic drugs). One patient died of leukemia relapse after 12 months of hematopoietic stem celltransplantation. The other three patients had disease-free survival until the time of fol ow-up.

Security of heterogeneous umbilical cord mesenchymal stem cells via intramuscular injection in Wistar rats / 中国组织工程研究

BACKGROUND:So far, the short-term changes of various organs after injection of umbilical cord mesenchymal stem cells have been reported, but there are few studies on the long-term changes of various organs in healthy rats after repeated intramuscular injection of umbilical cord mesenchymal stem cells. OBJECTIVE:To observe the security of intramuscular injection of heterogeneous umbilical cord mesenchymal stem cells. METHODS:Sixty male SPF Wistar rats were divided into six groups randomly:normal group (suspension liquid of umbilical cord mesenchymal stem cells);control group with culture solution;supernatant group (supernatant of human umbilical cord mesenchymal stem cells);low concentration group (0.25×105 human umbilical cord mesenchymal stem cells);moderate concentration group (1.0×105 human umbilical cord mesenchymal stem cells);high concentration group (4.0×105 human umbilical cord mesenchymal stem cells). Each rat was injected 0.8 mL liquid in muscle, 0.2 mL in each limb, twice at weeks 1 and 4. Biochemical tests were conducted before and after injection. At the end of 8 weeks, al the rats were kil ed and hematoxylin-eosin staining was done with the liver, spleen, lung, kidney, brain and muscle. RESULTS AND CONCLUSION:There was no abnormal change about biochemical tests and hematoxylin-eosin staining after the intramuscular injection of heterogeneous umbilical cord mesenchymal stem cells. No significant alteration was observed in the liver, spleen, lung, kidney, brain, and muscle of the limb after the injection of heterogeneous umbilical cord mesenchymal stem cells under suitable concentration. These findings indicate intramuscular injection of heterogeneous umbilical cord mesenchymal stem cells at certain concentrations is safe and reliable.

Construction of cardiac atrioventricular electrical conduction pathway by rabbit bone marrow mesenchymal stem cells / 中国组织工程研究

BACKGROUND:Autologous stem celltransplantation to the heart is a research direction of heart failure treatment, but there are relatively few of studies about autologous bone marrow mesenchymal stem celltransplantation targeting the cardiac conduction system. OBJECTIVE:To evaluate the potential of rabbit bone marrow mesenchymal stem cells for treatment of heart block. METHODS:Rabbit bone marrow mesenchymal stem cells were induced by 5-azacytidine to differentiate into cardiomyocyte-like cells. After thoracotomy, the left atrium-left ventricular anterior wal was sutured in 14 New Zealand white rabbits (8 in the experimental group and 6 in the control group). One month after the surgery, in the experimental group, autologous bone marrow mesenchymal stem cells induced by 5-azacytidine for 4 weeks were labeled with 4',6-diamidino-2-phenylindole and then injected into the suture area when opening the thoracic again. In the control group, cells cultured in medium were used. One month after celltransplantation, the third thoracotomy was done to insert electrodes into the left atrium and left ventricular anterior wal , for cardiac electrophysiological detection. Whether atrioventricular pathway formed in the suture area was observed. RESULTS AND CONCLUSION:After cells were transplanted into the sutured area, two rabbits in the experimental group were discovered to form the atrioventricular pathway in the sutured area through cardiac electrophysiological examination. After transplantation, transplanted cells were visible on the heart frozen sections under fluorescence microscope in the left ventricle and sutured area, but there was no cellin the control group. In the experimental group, bone marrow mesenchymal stem cells expressed Cx43 and formed gap junction intercellular communication with cardiomyocytes, which was presented as formation of the atrioventricular pathway on cardiac electrophysiology examination. These findings indicate that bone marrow mesenchymal stem cells can be used to treat cardiac conduction system block diseases.

Neural stem cell transplantation:its actuality and future used for treatment of hypoxic-ischemic encephalopathy / 中国组织工程研究

BACKGROUND:Many studies have showed that neural stem cells therapy is a new strategy for hypoxic-ischemic encephalopathy. OBJECTIVE:To review and analyze the status of research, transplantation strategies and mechanism of neural stem cells therapy for treatment of hypoxic-ischemic encephalopathy. METHODS:A computer-based retrieval was performed in PubMed and CNKI database to search papers published from August 2000 to August 2013 using the key words of“hypoxic-ischemic encephalopathy, neural stem cells”in English and Chinese. The papers with objective-independent and repetitive contents were excluded, and final y 39 papers were included for final analysis. RESULTS AND CONCLUSION:Neural stem celltransplantation can promote recovery of neurological function, which brings new hope to hypoxic-ischemic encephalopathy patients. But the study is at a primary stage and limited in laboratory. There are many critical factors that hinder the clinical transplantation, such as delivery path, transplantation time, single or combined transplantation, mechanisms of action. Application of neural stem cells requires further investigation.

Intracoronary transplantation of autologous peripheral blood stem cells in old patients with acute myocardial infarction:5-year postoperative evaluation of cardiac function / 中国组织工程研究

BACKGROUND:Myocardial infarction patients commonly appear to have left ventricular remodeling and heart failure. Because of physical characteristics, these two complications are more likely to occur in elderly patients with myocardial infarction. In recent years, stem celltransplantation in the treatment of acute myocardial infarction and heart failure has become a hot topic, and the feasibility and safety has been confirmed, but its long-term outcomes in elderly patients are stil unclear. OBJECTIVE:To assess the long-term effect of transplantation of autologous peripheral blood stem cells on the left ventricular remodeling and heart function in the old patients with myocardial infarction. METHODS:Thirty old patients (age ≥ 60 years) with myocardial infarction were randomly assigned to receive intracoronary transplantation of peripheral blood stem cells fol owing bone marrow cells mobilization by granulocyte colony-stimulating factor ( 300-600μg per day) subcutaneously for 5 days in addition to conventional therapy (standard drug therapy and percutaneous coronary intervention;transplantation group, n=15) or standard therapy (standard drug therapy and percutaneous coronary intervention;control group, n=15) . Complications during intervention, left ventricular function and left ventricular remodeling at baseline and 6, 12, 24, 60 months after treatment were monitored. RESULTS AND CONCLUSION:Left ventricular function, left ventricular end diastolic volume, and left ventricular end-systolic volume were significantly improved 6,12, 24, 60 months after autologous peripheral blood stem celltransplantation compared to baseline, while these parameters remained unchanged in the control group. These parameters had statistical difference between the two groups after treatment. During the fol ow-up, no severe side effects were observed. These findings indicate that autologous peripheral blood stem celltransplantation leads to significant and longstanding improvements in left ventricular performance of old patients with myocardial infarction, and shows good safety.

Effects of epimedium on osteogenic differentiation of bone marrow mesenchymal stem cells / 中国组织工程研究

BACKGROUND:Epimedium has been used in the treatment of osteoporosis and repair of bone defects. OBJECTIVE:To explore the effects of epimedium on the osteogenic differentiation of bone marrow mesenchymal stem cells. METHODS:A database search was performed to retrieve literatures addressing epimedium effects on the osteogenic differentiation of bone marrow mesenchymal stem cells. Then, the papers meeting the criteria were selected for in-depth analysis. During the osteogenic differentiation induced by epimedium, alkaline phosphatase, osteocalcin, osteopontin, transforming growth factorβ, bone morphogenetic proteins, osteocalcin, bone sialoprotein were detected in the bone marrow mesenchymal stem cells to understand the underlying mechanism of epimedium in proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. RESULTS AND CONCLUSION:Epimedium effects on bone marrow mesenchymal stem cells are shown in a dose-dependent manner. During the early induction, icari n can increase cellphosphatase activity;in the late induction, icari n can increase calcified nodules, promote osteocalcin secretion, significantly improve the expressions of transforming growth factorβ1, bone morphogenetic protein 2, insulin-like growth factor-1, osteopontin and bone sialoprotein. Epimedium, which can be used as an excellent osteoinductive factor, improves the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.

Therapeutic applications of umbilical cord mesenchymal stem cells in Parkinson’s disease / 中国组织工程研究

BACKGROUND:Animal experiments have repeatedly verified that umbilical cord stem celltransplantation can improve the rotational behavior of rats with Parkinson’s disease, with lower immune rejection response. OBJECTIVE:To evaluate the therapeutic effects of human umbilical cord mesenchymal stem celltransplantation in the treatment of Parkinson’s disease using the Unified Parkinson’s Disease Rating Scale. METHODS:Fifteen patients with Parkinson’s disease were enrol ed, including 8 males and 7 females, aged 52-76 years. Hoehn&Yahr staging was 3-5. After informed consent was obtained from puerperae and the procedure was approved by the hospital ethics committee, ful-term maternal umbilical cord was aseptical y col ected, to culture umbilical cord mesenchymal stem cells. Al patients were hospitalized, and treated with human umbilical cord mesenchymal stem celltransplantation via carotid artery puncture. Neurological function of patients was assessed using a comprehensive rating scale for Parkinson’s disease before and 1 month after cells transplantation. Higher score indicated more severe neurological deficits. RESULTS AND CONCLUSION:Fifteen patients entered the result analysis. Compared with before transplantation, 15 patients showed significantly lowered scores on the Unified Parkinson’s Disease Rating Scale at 1 month after transplantation (P<0.05). The improvement was mainly concentrated in the tremor and rigidity, but bradykinesia and unstable position were not improved. Graft versus host disease did not occur in al 15 cases. These findings indicate that umbilical cord blood mesenchymal stem celltransplantation for treating Parkinson’s disease has obvious curative effects and significantly improves neurological functions.

Different sources of mesenchymal stem cells in the treatment of liver fibrosis in rats / 中国组织工程研究

BACKGROUND:In recent years, studies have shown that mesenchymal stem cells can secrete various growth factors, and has certain application prospect in the treatment of liver fibrosis. OBJECTIVE:To explore the different sources of mesenchymal stem cells in the treatment of liver fibrosis in rats. METHODS:Fifty Sprague-Dawley rats were given intraperitoneal injection of carbon tetrachloride to construct the model of liver fibrosis. Another 10 normal Sprague-Dawley rats were used as normal controls. Model rats were randomly divided into five groups, 10 rats in each group, including model control group, normal saline group, bone marrow mesenchymal stem cellgroup, umbilical cord mesenchymal stem cellgroup, and umbilical cord blood mesenchymal stem cellgroup. After 8 weeks of modeling, different sources of mesenchymal stem cells at a density of 2×106 were injected via tail vein into model rats. After 12 weeks, the rats were kil ed, and serum alanine aminotransferase, aspartate aminotransferase and albumin levels were detected as wel as the expression of type I col agen and glial fibril ary acidic protein in liver tissue was detected by fluorescence quantitative PCR method. RESULTS AND CONCLUSION:We have successful y established the SD rat model of hepatic fibrosis. Bone marrow mesenchymal stem cells aggravated hepatic fibrosis, umbilical cord blood and umbilical cord mesenchymal stem cells could reduce the level of hepatic fibrosis in rats. Umbilical cord mesenchymal stem cells had the most obvious effect that significantly reduced expressions of alanine aminotransferase, aspartate aminotransferase and type I col agen and glial fibril ary acidic protein. The results showed different sources of mesenchymal stem cells have different effects on rat fibrosis. Bone marrow mesenchymal stem cells aggravate hepatic fibrosis, and umbilical cord and umbilical cord blood stem cells can al eviate hepatic fibrosis in rats.